rs200893856
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS1_Supporting
The NM_005076.5(CNTN2):c.821G>A(p.Arg274His) variant causes a missense change. The variant allele was found at a frequency of 0.0000837 in 1,612,488 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R274C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005076.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN2 | NM_005076.5 | c.821G>A | p.Arg274His | missense_variant | 8/23 | ENST00000331830.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN2 | ENST00000331830.7 | c.821G>A | p.Arg274His | missense_variant | 8/23 | 1 | NM_005076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000128 AC: 32AN: 249638Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 134942
GnomAD4 exome AF: 0.0000815 AC: 119AN: 1460328Hom.: 1 Cov.: 31 AF XY: 0.0000991 AC XY: 72AN XY: 726294
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.821G>A (p.R274H) alteration is located in exon 8 (coding exon 7) of the CNTN2 gene. This alteration results from a G to A substitution at nucleotide position 821, causing the arginine (R) at amino acid position 274 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Epilepsy, familial adult myoclonic, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 274 of the CNTN2 protein (p.Arg274His). This variant is present in population databases (rs200893856, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CNTN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 474492). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CNTN2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at